What are the treatment options for a patient with Premenstrual Dysphoric Disorder (PMDD)?

Treatment for Premenstrual Dysphoric Disorder (PMDD)

Selective serotonin reuptake inhibitors (SSRIs) are the first-line treatment for PMDD, with continuous dosing more effective than luteal-phase-only administration. 1, 2, 3

First-Line Pharmacological Treatment: SSRIs

SSRIs demonstrate the strongest evidence for efficacy in PMDD, reducing overall premenstrual symptoms with moderate-certainty evidence (SMD -0.57). 2 The following SSRIs are FDA-approved or well-studied for PMDD:

• Sertraline 50-150 mg/day 4, 5
• Fluoxetine 10-20 mg/day 4, 5
• Escitalopram 10-20 mg/day 4
• Paroxetine 12.5-25 mg/day 4, 5

Dosing Strategy

Continuous daily administration is more effective than luteal-phase-only dosing (continuous: SMD -0.69 vs. luteal phase: SMD -0.39; P = 0.03 for subgroup difference). 2 However, SSRIs can be effective when used cyclically during the luteal phase only or even limited to the duration of monthly symptoms, unlike their use in depression where daily administration is required. 6

Second-Line Pharmacological Treatment: Hormonal Contraceptives

Drospirenone-containing oral contraceptives (drospirenone 3 mg + ethinyl estradiol 20 mcg) are FDA-approved for PMDD treatment and should be considered as first or second-line therapy, particularly in women desiring contraception. 1, 4, 3

Critical Contraindications for Drospirenone

Do not prescribe drospirenone to patients with: 1

• Renal impairment
• Adrenal insufficiency
• High risk of arterial or venous thrombotic disease
• Women over 35 years who smoke

Monitor serum potassium during the first treatment cycle in women on long-term medications that increase potassium (NSAIDs, potassium-sparing diuretics, ACE inhibitors, angiotensin-II receptor antagonists, aldosterone antagonists, heparin). 1

First-Line Non-Pharmacological Treatment: Cognitive Behavioral Therapy

Cognitive behavioral therapy (CBT) reduces functional impairment, depressed mood, anxiety, mood swings, irritability, and symptom severity in PMDD. 4, 3 CBT can be used as monotherapy or combined with pharmacotherapy, with evidence showing reduction in: 4

• Functional impairment and impact on daily life
• Depressed mood and feelings of hopelessness
• Anxiety and mood swings
• Irritability and sensitivity
• Insomnia and conflict with others

Alternative Treatments with Supporting Evidence

Calcium supplementation (1200 mg/day) has demonstrated consistent therapeutic benefit and should be considered as an adjunct treatment. 5, 6, 3

Other options with some evidence include: 5, 6, 3

• Chasteberry (Vitex agnus castus) - may be useful as adjunct
• St. John's wort (Hypericum perforatum) - may be useful as adjunct, but monitor for drug interactions with SSRIs

Additional Pharmacological Options

For patients who fail SSRI therapy: 5

• Venlafaxine (SNRI)
• Duloxetine (SNRI)
• Alprazolam (benzodiazepine - use with caution due to dependence risk)
• Buspirone (anxiolytic)

Common Adverse Effects of SSRIs

Patients should be counseled about expected adverse effects, which occur in a substantial proportion of users: 2

• Nausea (OR 3.30) - most common
• Asthenia/decreased energy (OR 3.28)
• Somnolence/decreased concentration (OR 3.26)
• Sexual dysfunction/decreased libido (OR 2.32)
• Insomnia (OR 1.99)
• Dizziness (OR 1.96)

Treatment Algorithm

1. Confirm diagnosis with prospective daily symptom charting for at least two menstrual cycles to document luteal-phase symptoms that resolve with menses 6, 3

2. Initiate SSRI therapy (sertraline, fluoxetine, escitalopram, or paroxetine) with continuous daily dosing as first choice 4, 2, 3

3. If patient desires contraception or has contraindications to SSRIs, consider drospirenone-containing oral contraceptive after screening for contraindications 1, 4, 3

4. Add CBT either as monotherapy or combined with pharmacotherapy 4, 3

5. If inadequate response after 2-3 menstrual cycles, consider:

   • Switching to alternative SSRI 5
   • Switching to SNRI (venlafaxine or duloxetine) 5
   • Adding calcium supplementation if not already implemented 6, 3

6. For refractory cases, consider ovulation suppression with GnRH agonists or other hormonal methods 3

Critical Pitfalls to Avoid

Do not confuse PMDD with premenstrual syndrome (PMS) - PMDD requires significant functional impairment and specific DSM-5 criteria including at least 5 symptoms with at least one being affective (depressed mood, anxiety, mood lability, or irritability). 1, 4

Do not prescribe drospirenone without screening for hyperkalemia risk factors and checking potassium in the first treatment cycle for at-risk patients. 1

Do not assume SSRIs require 4-6 weeks to work in PMDD - unlike depression, symptom-onset dosing or luteal-phase dosing can provide rapid benefit within days. 6